Mechanical Embolus Removal In Cerebral Ischemia Research Articles

Changing Management of Acute Ischaemic Stroke: the New Treatments and Emerging Role of Endovascular Therapy.

Urgent reperfusion of the ischaemic brain is the aim of stroke treatment, and the last two decades have seen a rapid advancement in the medical and endovascular treatment of acute ischaemic stroke. Intravenous tissue plasminogen activator (tPA) was first introduced as a safe and effective thrombolytic agent followed by the introduction of newer thrombolytic agents as well as anticoagulant and antiplatelet agents, proposed as potentially safer drugs with more favourable interaction profiles. In addition to chemo-thrombolysis, other techniques including transcranial sonothrombolysis and microbubble cavitation have been introduced which are showing promising results, but await large-scale clinical trials. These developments in medical therapies which are undoubtedly of great importance due to their potential widespread and immediate availability are paralleled with gradual but steady improvements in endovascular recanalisation techniques which were initiated by the introduction of the MERCI (Mechanical Embolus Removal in Cerebral Ischemia) and Penumbra systems. The introduction of the Solitaire device was a significant achievement in reliable and safe endovascular recanalisation and was followed by further innovative stent retrievers. Initial trials failed to show a solid benefit in endovascular intervention compared with IV-tPA alone. These counterintuitive results did not last long, however, when a series of very well-designed randomised controlled trials, pioneered by MR-CLEAN, EXTEND-IA and ESCAPE, emerged, confirming the well-believed daily anecdotal evidence. There have now been seven positive trials of endovascular treatment for acute ischaemic stroke. Now that level I evidence regarding the superiority of endovascular recanalisation is abundantly available, the clinical challenge is how to select patients suitable for intervention and to familiarise and educate stroke care providers with this recent development in stroke care. It is important for the interventional services to be provided only in comprehensive stroke centres and endovascular interventions attempted by experienced well-trained operators, at this stage as an adjunct to the established medical treatment of IV-tPA, if there are no contraindications.

Admission Motor Strength Grade Predicts Mortality in Patients with Acute Ischemic Stroke Undergoing Mechanical Thrombectomy

Background: The mortality due to mechanical thrombectomy (MT) in the acute treatment of intracranial arterial occlu- sions can be up to 45%. The SWIFT (Solitaire FR with the Intention for Thrombectomy) and Multi MERCI (mechani- cal embolus removal in cerebral ischemia) trials have evaluated the safety and efficacy of MT. It may be important to determine pre-procedural factors that help predict post-intervention prognosis. We sought to determine if admission medical research council (MRC) motor strength grade along with other factors can be used as predictor of mortality after MT for acute ischemic stroke. Methods: Retrospective analysis of stroke database assessing outcomes in all 62 patients who underwent MT as an intervention for acute ischemic stroke, with or without concurrent intravenous thrombolysis was done. Five baseline variables were included in univariate and multivariate analyses to define the in- dependent predictors of mortality during current hospitalization. The medical research council (MRC) motor grade (0 - 5); modified collateral flow (CS) grading (0 - 3); age; acute and chronic co-morbidities were used as the baseline vari- ables. If motor strength grade were different in upper and lower extremities, then the lower grade was used. Age was analyzed independently as well as dichotomized using 80 as cut-off value. Relevant stroke related acute and chronic co-morbidities were given 1 point each and mean calculated. Results: In the univariate analysis, low (0 - 1) motor strength grade (OR, 0.11; 95% CI, 0.021 - 0.33; p = 0.001) and age (OR, 1.06; 95% CI, 1.02 - 1.12; p = 0.011) was sig- nificantly associated with mortality. The presence of collateral flow, acute and chronic co-morbidities were not signifi- cantly associated with mortality. In the multivariate analysis, motor grade retained its statistical significance for morta- lity (OR, 0.09; 95% CI, 0.01 - 0.32; p = 0.003) along with chronic co-morbidity (OR, 1.52; 95% CI 1.05 - 2.43; p

The Totaled Health Risks in Vascular Events (THRIVE) Score Predicts Ischemic Stroke Outcomes Independent of Thrombolytic Therapy in the NINDS tPA Trial

To date, no ischemic stroke outcome prediction scores have been validated for use in the setting of both endovascular and non-endovascular stroke treatments. The Totaled Health Risks in Vascular Events (THRIVE) score has been previously validated in patients undergoing endovascular stroke treatment, and we hypothesized that it would perform similarly well in patients receiving intravenous tissue plasminogen activator (tPA) or no acute therapy. We compared the performance of the THRIVE score between patients in the National Institutes of Neurological Disorders and Stroke (NINDS) tPA trial and patients in the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) trials of endovascular stroke treatment. The predictive performance of the THRIVE score was compared using receiver operator characteristic (ROC) curve analysis. In the NINDS cohort, separate analyses were also performed for patients receiving tPA versus those receiving placebo. ROC curve analysis revealed a good prediction of outcomes across the range of THRIVE scores in both the NINDS and MERCI datasets. As we have previously found in the MERCI datasets, the THRIVE score, which encompasses the National Institutes of Health Stroke Scale (NIHSS) score, age, and chronic disease burden, was a better predictor of outcomes than NIHSS and age alone in the NINDS trial dataset. THRIVE score and tPA administration both strongly predicted outcome, but these effects were statistically independent. The THRIVE score provides accurate prediction of long-term neurologic outcomes in patients with acute ischemic stroke regardless of treatment modality. Both the THRIVE score and tPA administration predict outcome, but the THRIVE score does not influence the impact of tPA on outcome, and tPA administration does not influence the impact of THRIVE score on outcome.

Validation of the Totaled Health Risks in Vascular Events (THRIVE) Score for Outcome Prediction in Endovascular Stroke Treatment

We recently developed the Totaled Health Risks In Vascular Events (THRIVE) score to predict outcomes after endovascular stroke treatment. The THRIVE score, which incorporates age, National Institutes of Health Stroke Scale score, and three medical comorbidities (hypertension, diabetes mellitus, and atrial fibrillation), was developed using data from the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials. We set out to perform external validation of the THRIVE score using data from the largest registry of endovascular stroke treatment performed to date, the Merci Registry. We compared the performance of the THRIVE score in two different data sets: the development cohort (the MERCI and Multi MERCI trials, n = 305) and a validation cohort (the Merci Registry, a prospective multicenter registry of patients undergoing endovascular stroke treatment, n = 1000). We examined the predictive utility of the THRIVE score across the range of clinical outcomes and used receiver-operator characteristics curve analysis to compare score performance in the two data sets. The THRIVE score predicted good outcome, death, and the full range of the modified Rankin Scale in a similar fashion between the MERCI trials and the Merci Registry. Receiver-operator characteristics curve comparisons showed no statistically significant difference in the performance of the THRIVE score between the two data sets: for good outcome, the receiver-operator characteristics area under the curve was 0·293 for the MERCI trials and 0·266 for the Merci Registry (P = 0·47) and for death, the receiver-operator characteristics area under the curve was 0·692 for the MERCI trials and 0·717 for the Merci Registry (P = 0·48). The THRIVE score and vessel recanalization were also found to be independent and unrelated predictors of clinical outcome. The THRIVE score reliably predicts outcomes after endovascular stroke treatment and may be useful as a clinical prognostic tool and to perform severity adjustments in stroke clinical research.

Abstract 162: Rescue Carotid Stenting To Reestablish Flow In The Middle Cerebral Artery And Anterior Cerebral Artery In Patients Who Present With Acute Ischemic Stroke And Carotid Occlusion

Introduction: Acute ischemic stroke due to the occlusion of the internal carotid artery (ICA) is associated with malignant stroke and poor outcome. Without revascularization of ICA, perfusion to the middle cerebral artery (MCA) and anterior cerebral artery (ACA) is not possible. Objective: Objective of our study is to evaluate the technical feasibility of emergent extracranial carotid artery revascularization using stent and to evaluate the impact of stenting in distal cerebral perfusion. Method: From an established stroke database consecutive patients with acute ischemic stroke who underwent emergent extracranial carotid artery stenting and thrombolysis/clot retrieval of the MCA and ACA from July 2007 to December 2008 were enrolled. Patients’ demographics including presenting National Institute of Health Stroke Scale (NIHSS), degree of revascularization, hemorrhagic conversion and 30 days outcome data using Glasgow Outcome Scale (GOS) were collected. Result: Successful ICA stenting was possible in 20/21 (95%) patients. The mean age of patients was 62 plus-minus 15 years and mean NIHSS was 18 plus-minus 5. Carotid stenting facilitated successful revascularization of the MCA and ACA using TPA (tissue plasminogen activator) and MERCI (mechanical embolus removal in cerebral ischemia) clot retriever device in 18 patients (85.7%), 14 (67%) of which has achieved complete recanalization in the MCA and ACA. In complete recanalization group, a 4 point or higher NIHSS improvement was observed in 11/14 (78.5%) patients. Symptomatic intracranial hemorrhage was observed in 9.5% patients. Seven (50%) of 14 patients who achieved complete recanalization had a good outcome. Five (71%) of 7 patients who did not achieve complete recanalazation of the MCA and ACA died and had NIHSS 20 or higher. NIHSS 20 or higher was associated with incomplete recanalization of the MCA and ACA and poor outcome. Conclusion: Emergent extracranial carotid artery revascularization using stent is not only technically feasible in patients with acute ischemic stroke who present with acute carotid artery occlusion, but it also facilitates successful reestablishment of flow in the MCA and ACA with good outcome. Further study is necessary.

Pharmacological and non-pharmacological recanalization strategies in acute ischemic stroke.

According to the guidelines of the European Stroke Organization (ESO) and the American Stroke Association (ASA), acute stroke patients should be managed at stroke units that include well organized pre- and in-hospital care. In ischemic stroke the restoration of blood flow has to occur within a limited time window that is accomplished by fibrinolytic therapy. Newer generation thrombolytic agents (alteplase, pro-urokinase, reteplase, tenecteplase, desmoteplase) have shorter half-life and are more fibrin-specific. Only alteplase has Food and Drug Administration (FDA) approval for the treatment of acute stroke (1996). The National Institute of Neurological Disorders and Stroke (NINDS) trial proved that alteplase was effective in all subtypes of ischemic strokes within the first 3 h. In the European cooperative acute stroke study III trial, intravenous (IV) alteplase therapy was found to be safe and effective (with some restrictions) if applied within the first 3–4.5 h. In middle cerebral artery (MCA) occlusion additional transcranial Doppler insonication may improve the breakdown of the blood clot. According to the ESO and ASA guidelines, intra-arterial (IA) thrombolysis is an option for recanalization within 6 h of MCA occlusion. Further trials on the IA therapy are needed, as previous studies have involved relatively small number of patients (compared to IV trials) and the optimal IA dose of alteplase has not been determined (20–30 mg is used most commonly in 2 h). Patients undergoing combined (IV + IA) thrombolysis had significantly better outcome than the placebo group or the IV therapy alone in the NINDS trial (Interventional Management of Stroke trials). If thrombolysis fails or it is contraindicated, mechanical devices [e.g., mechanical embolus removal in cerebral ischemia (MERCI)- approved in 2004] might be used to remove the occluding clot. Stenting can also be an option in case of acute internal carotid artery occlusion in the future. An intra-aortic balloon was used to increase the collateral blood flow in the Safety and Efficacy of NeuroFlo™ Technology in Ischemic Stroke trial (results are under evaluation). Currently, there is no approved effective neuroprotective drug.

Effects of Sex on Mechanical Embolectomy Outcome

Given that women have demonstrated a greater margin of benefit than men from treatment with thrombolytics in certain acute stroke trials, the current study explored whether this sex effect extends to mechanical embolectomy and can be explained by revascularization rate. The study included the 305 patients enrolled in the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials. Demographic, risk factor, and procedural characteristics were evaluated in women and men. Odds ratios for outcomes by sex were compared in patients with revascularization and those without revascularization, defined as a Thrombolysis in Myocardial Infarction score of 2-3 at the end of the procedure. Outcomes included a modified Rankin Scale (mRS) score of 0-2 and mortality at 90 days, as well as the presence of symptomatic intracranial hemorrhage (sICH). Patient and procedural characteristics did not differ between women and men except for mean age (women, 70.1 years; men, 64.8 years; P = .003), hypertension (women, 78.0%; men, 65.5%; P = .021), and number of vertebrobasilar occlusions (women, 8/159 [5.0%]; men, 20/146 [13.7%]; P = .01). Revascularization was significantly associated with favorable outcomes in both women and men (P < .0001), and rates of favorable outcome, mortality, and sICH did not differ between women and men when the vessel was revascularized. Likewise, mechanical embolectomy with the Merci Retriever was not associated with different outcomes in women and men when the vessel was revascularized. Our data suggest that the sex differences seen in thrombolytic trials might be due to factors other than immediate postprocedural large vessel opening.

Endovascular Thrombectomy for Acute Ischemic Stroke in Failed Intravenous Tissue Plasminogen Activator Versus Non–Intravenous Tissue Plasminogen Activator Patients

Intracranial mechanical thrombectomy is a therapeutic option for acute ischemic stroke patients failing intravenous tissue plasminogen activator (IV tPA). We compared patients treated by mechanical embolus removal in cerebral ischemia (MERCI) thrombectomy after failed IV tPA with those treated with thrombectomy alone. We pooled MERCI and Multi MERCI study patients, grouped them either as failed IV tPA or non-IV tPA, and assessed revascularization rates, procedural complications, symptomatic hemorrhage rates, clinical outcomes, and mortality. We also evaluated outcomes stratified by the occlusion site and final revascularization. Among 305 patients, 48 failed, and 257 were ineligible for IV tPA. Nonresponders to IV tPA trended toward a higher revascularization rate (73% versus 63%) and less mortality (27.7% versus 40.1%) and had similar rates of symptomatic hemorrhage and procedural complications. Favorable 90-day outcomes were similar in failed and non-IV tPA patients (38% versus 31%), with no difference according to occlusion site. Among patients failing IV tPA, good outcomes tended to occur more frequently in revascularized patients (47.1% versus 15.4%), although this relationship was attributable solely to middle cerebral artery and not internal carotid artery occlusions, with no difference in mortality. Among IV tPA-ineligible patients, revascularization correlated with good outcome (47.4% versus 4.4%) and less mortality (28.5% versus 59.6%). The risks of hemorrhage and procedure-related complications after mechanical thrombectomy do not differ with respect to previous IV tPA administration. Thrombectomy after IV tPA achieves similar rates of good outcomes, a tendency toward lower mortality, and similar revascularization rates when stratified by clot location. Good outcomes correlate with successful revascularization except with internal carotid artery occlusions in tPA-nonresponders.

Clinical Outcomes in Middle Cerebral Artery Trunk Occlusions Versus Secondary Division Occlusions After Mechanical Thrombectomy

The benefit of endovascular revascularization of patients with acute ischemic stroke with middle cerebral artery (MCA) secondary division (M2) occlusions as compared with MCA trunk (M1) occlusions is not known. In this analysis, we compared revascularization status and clinical outcomes in patients with angiographically confirmed MCA M1 versus isolated M2 occlusions treated with mechanical thrombectomy using the Merci Retriever devices. We retrospectively analyzed the pooled data of patients with MCA strokes from the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials. Patient data were dichotomized into 2 groups: MCA M1 occlusions and isolated M2 occlusions. Baseline characteristics, revascularization rates, hemorrhage rates, complications, outcomes, and mortality were evaluated for both groups. Of 178 patients with MCA occlusion treated in the MERCI and Multi MERCI trials, 84.3% had M1 lesions and 15.7% had isolated M2 lesions. Patients with isolated M2 occlusions were revascularized at a higher rate, required a lower mean number of passes, and were associated with a trend toward shorter mean procedure time than patients with M1 occlusions. No statistically significant differences were found between M2 and M1 groups for symptomatic hemorrhage, clinically significant procedural adverse events, favorable 90-day outcome, or 90-day mortality, although in all instances, the M2 outcomes were numerically better than those in M1 subjects. In multivariate analysis, final revascularization was the strongest independent predictor of good outcome at 90 days. Patients with both MCA M1 occlusions and isolated M2 occlusions can achieve a relatively high rate of revascularization and favorable clinical outcomes after mechanical thrombectomy. In fact, patients with isolated M2 occlusions had a higher rate of revascularization, required fewer passes, and had no increased complications compared with patients with M1 occlusions.

Futile Recanalization in Mechanical Embolectomy Trials

See related article, pages 953–960. It is well known that clot burden is likely a major determinant of vessel recanalization rates with the volume of thrombus to be dissolved by fibrinolytic agents much larger in the intracranial carotid artery than in the middle cerebral artery. So, the more distal the occlusion is located, the higher the likelihood of recanalization. This statement seems to be true for intravenous thrombolysis as demonstrated in several transcranial Doppler studies showing that the probability of complete recanalization at 2 hours of tissue plasminogen activator (tPA) bolus is 44%, 29%, and 10% in the distal middle cerebral artery, proximal middle cerebral artery, and terminal internal carotid artery, respectively.1 However, a differential treatment response according to clot size and location has not been demonstrated in patients with stroke undergoing mechanical embolectomy. Several methodological, technical, and pathophysiological differences preclude the translation of this “clot-burden effect” of intravenous tPA therapy into mechanical revascularization trials. In this issue of Stroke, Shi et al2 retrospectively analyzed the pooled data of patients with middle cerebral artery strokes from the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials. Patients were dichotomized into 2 groups: middle cerebral artery M1 occlusions and isolated M2 occlusions. Baseline characteristics, revascularization rates, hemorrhage rates, complications, outcomes, and mortality were evaluated for both groups. The authors observed that patients with isolated M2 occlusions were revascularized at a higher rate (82.1% versus 60%), required fewer number of passes, and were associated with a trend of a shorter median procedure time than patients with M1 occlusions. However, no statistically significant differences were …

Devices and drugs for stroke: why do regulations differ?

Devices and drugs for stroke: why do regulations differ?

Predictors of Good Clinical Outcomes, Mortality, and Successful Revascularization in Patients With Acute Ischemic Stroke Undergoing Thrombectomy

The Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials evaluated the safety and efficacy of thrombectomy in the treatment of intracranial arterial occlusions within 8 hours of symptom onset. We sought to determine the predictors of clinical and angiographic outcomes in these patients. The trial cohorts were combined in a data set of 305 patients. Twenty-eight baseline variables were included in univariate and multivariate analyses to define the independent predictors of good outcomes (modified Rankin Scale score </=2), mortality, and successful revascularization (Thrombolysis In Myocardial Ischemia 2 to 3 flow). In the univariate analysis, final revascularization, baseline National Institutes of Health Stroke Scale, age, and systolic blood pressure were associated with both good outcomes and mortality at 90 days (P<0.0018 for all). In the multivariate analysis, final revascularization (OR, 20.4; 95% CI, 7.7 to 53.9; P<0.0001), baseline National Institutes of Health Stroke Scale (OR, 0.86; 95% CI, 0.81 to 0.92; P<0.0001), and age (OR, 0.96; 95% CI, 0.95 to 0.98; P=0.0004) were independent predictors of good outcome. Final revascularization (OR, 0.28; 95% CI, 0.16 to 0.50; P<0.0001), baseline National Institutes of Health Stroke Scale score (odds ratio, 1.09; 95% CI, 1.04 to 1.14; P=0.0001), age (OR, 1.05; 95% CI, 1.03 to 1.07; P<0.0001), and internal carotid artery occlusion (OR, 2.17; 95% CI, 1.22 to 3.86; P=0.0084) were the strongest predictors of mortality. Systolic blood pressure (<150 versus >or=150 mm Hg; OR, 0.42; 95% CI, 0.26 to 0.70; P=0.0007) and M2 occlusion (OR, 3.86; 95% CI, 1.28 to 11.67; P=0.0168) were independent predictors of revascularization. Final recanalization status represents the strongest predictor of clinical outcomes in patients undergoing thrombectomy. The ability to remove the clot is negatively influenced by systolic blood pressure on presentation perhaps because of the hydraulic forces imposed by higher blood pressures. Although internal carotid artery occlusions are associated with increased mortality, they do not appear to influence the chances of good outcomes. This finding supports the inclusion of internal carotid artery occlusions in future efficacy trials.

Atherosclerotic Peripheral Vascular Disease Symposium II

Stroke is the third leading cause of death and a leading cause of adult disability in the United States.1 From a global perspective, stroke is also a leading cause of death and disability. The past 20 years have seen significant improvements in stroke prevention, yet each year, >700 000 people have a new or recurrent stroke.2,3 The medical and societal costs of stroke exceed $62 billion in the United States alone.4 Any intervention that could reverse or limit the effects of a stroke would have dramatic medical, societal, and public health benefits. This section will focus on treatment of acute ischemic stroke, which accounts for 80% to 85% of all strokes. Other recent publications have focused on therapies for intracerebral hemorrhage. Acute interventions to reduce the effects of an ischemic stroke can be organized into several main approaches: (1) reperfusion strategies (lytics, endovascular/mechanical); (2) neuroprotection; and (3) restoration, regeneration, and rehabilitation. ### Medical Therapies Thrombolytic therapies for acute ischemic stroke have been used or under study for 30 to 40 years, yet only recently has an agent been approved by the US Food and Drug Administration (FDA) and included in the treatment guidelines. Intravenous recombinant tissue plasminogen activator (rtPA) is the only FDA-approved medical therapy proven to reduce the effects of an ischemic stroke.5,6 Its main mechanism of action is to lyse a clot that is occluding a cerebral vessel, thereby reperfusing distal ischemic brain tissue and preventing or limiting the area of cell death and tissue necrosis. The efficacy of intravenous rtPA was proven in the pivotal National Institute of Neurological Disorders and Stroke (NINDS) rtPA study, which showed improved outcomes for patients treated within 3 hours of stroke onset.7 The NINDS tissue plasminogen activator (tPA) trial had an efficacy end point that was equivalent to the …

Vertebrobasilar Revascularization Rates and Outcomes in the MERCI and Multi-MERCI Trials

Mortality of 40% to 86% and good outcomes in only 13% to 21% of patients beg for treatment options for basilar occlusion. This study determined outcomes of patients with vertebrobasilar occlusion treated with mechanical embolus removal in cerebral ischemia (MERCI) retriever mechanical thrombectomy. Patients with vertebrobasilar occlusion in the MERCI and Multi-MERCI trials received treatment up to 8 hours after symptom onset. Recanalization was determined after retriever use and adjunctive therapy. Mortality and good outcomes, modified Rankin scale score 0-3, were determined at 90 days in patients who were recanalized and not recanalized. Recanalization occurred in 21 of 27 (78%) patients. Mortality was 44% and good outcomes were seen in 41%. Patients with recanalization tended to have better outcomes than those without. Outcomes in patients with vertebrobasilar occlusions treated with the MERCI retriever compared favorably with natural history reports and tended to be better in those patients with recanalization.

Acute endovascular stroke therapy

A decade after the US Food and Drug Administration (FDA) approved intravenous tissue plasminogen activator for treatment of acute ischemic stroke, the public health impact of this treatment on stroke outcome remains limited. The extremely small time window for treatment and very low recanalization rates in large artery strokes are its major shortcomings. Endovascular therapies for the treatment of acute stroke have rapidly evolved during this time period and may overcome these limitations. FDA approval of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) concentric retriever in August 2004 for the treatment of occluded brain arteries has spurred trials of newer devices for mechanical thrombolysis in acute stroke. At present, there are two major National Institutes of Health-sponsored randomized controlled trials testing endovascular treatments in acute stroke. In this article, we provide an experience-guided review of the current approach to the endovascular treatment of acute ischemic stroke and current evidence for various strategies. We first emphasize the key aspects of patient selection, including the increasingly central role of perfusion/diffusion imaging. The technical aspects of chemical, mechanical, ultrasound-based, and multimodal approaches are provided along with the authors' own experiences. Most of the endovascular modalities tested in clinical trials show recanalization rates in the range of 50% to 65%. However, no one modality is clearly superior. In practice, multimodal treatment strategy is often employed to achieve rapid recanalization of occluded cerebral vessels and minimize chances of hemorrhage. This may become the standard of care in the future.

Does the Merci Retriever Work?

In a decade after approval of IV rt-PA for acute stroke, treatment leads to good outcomes in less than half of patients, and hemorrhage rates have not been reduced. Recanalization improves outcome1 but is often delayed and incomplete. Devices offer the promise of rapid recanalization with a greater proportion of good outcomes and fewer hemorrhages. The Merci retrieval system was introduced with hopes of fulfilling this promise. The FDA recently approved this device for removal of thrombus from intracranial arteries in patients with stroke. Despite this approval, the question of whether the device works remains unsettled. The recently published Mechanical Embolus Removal in Cerebral Ischemia (MERCI) trial2 using the Merci retriever claims efficacy based on a recanalization rate that is greater than the spontaneous recanalization rate observed in the Prolyse in Acute Cerebral Thromboembolism (PROACT) II trial control group.3 Recanalization …

Does the Merci Retriever Work?

Section Editors: Geoffrey A. Donnan MD, FRACP Stephen M. Davis MD, FRACP Technically, it works. And remarkably so. The Merci Retriever is a mechanical embolectomy device designed to reopen occluded vessels by extracting occlusive thrombi from the cerebral vasculature. In the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) trial (parts I and II combined), among 151 patients enrolled in the intention-to-treat group; partial or complete recanalization by use of the device alone was achieved in 46%.1 This rate substantially exceeded that in the prespecified comparator group—patients enrolled in the control arm of the Prolyse in Acute Cerebral Thromboembolism (PROACT-II) trial (18%). The associated probability value of <0.0001 indicates a less than 1 in 10 000 chance that this result occurred by chance. The Merci Retriever indeed works. And it works well where we most need it to work: on proximal occlusions for which there was previously no good therapy. Proximal carotid terminus and M1 middle cerebral artery thrombi respond poorly to IV or intra-arterial fibrinolytic therapy, likely attributable in large part to the sheer volume of the clot burden requiring enzymatic digestion. The average volume of carotid terminus thrombi (0.4 ml) is more than an order of magnitude larger than that of M2 middle cerebral artery division thrombi …

Editorial Comment—Mechanical Embolus Removal

We must applaud the resourceful inventors, manufacturer, and investigators of the Merci Retriever device for completing the decade-long odyssey of directing the device through the design, development, study, and Food and Drug Administration (FDA) approval process. A number of devices have failed to climb that hill, falling back in pilot trials despite enthusiasm for their potential. However, previous editorials regarding approval of devices in general, and the potential Pandora’s box of approval of the Merci Retriever in particular,1,2,3⇓⇓dictate that we evaluate the data that gained its approval as an embolectomy and revascularization device, as finally presented in this journal. The device is intended to restore blood flow in the neurovasculature by removing thrombus in patients experiencing ischemic stroke.4 The manuscript gives no confirmation that flow restoration in this study is due to thrombus removal (embolectomy), as opposed to clot disruption with proximal revascularization and distal embolization. Aggressive clot manipulation more quickly opens primary occlusions with fibrinolytic agent.5,6⇓ No substantive data on wire-based clot manipulation without lytic therapy exists. An abstract from the February 2005 issue of Stroke suggested 50% subject clot removal with use of the Merci device.7 It was suggested that the 50% who might have a clot removed will be the same 50% that recanalize, and therefore that those who improve are among the 50% with clot removal. Nevertheless, even at that level of effectiveness, it is unclear that the device is doing what it is approved to do, which is to remove clots dependably. This embolectomy and/or revascularization issue seems a regulatory Scylla-and-Charybdis issue that might be of lesser import if clinical trial outcomes had been more impressive. The primary Mechanical Embolus Removal in Cerebral Ischemia (MERCI) study outcome was the rate of recanalization of the terminal internal carotid …

Mechanical Embolus Removal. A New Day Dawning

Mechanical Embolus Removal. A New Day Dawning

Approval of the MERCI Clot Retriever

Section Editors: Marc Fisher MD Antoni Davalos MD The Food and Drug Administration (FDA) evaluates applications for new human drugs, biologics, and complex medical devices. Companies must obtain FDA approval to legally market these products. In August, the FDA gave Concentric Medical clearance to market its Merci Retriever system to “remove blood clots from the brain in patients experiencing an ischemic stroke.” Given that the FDA is charged with “protecting the public health by assuring the safety, efficacy, and security of… biological products and medical devices…, ” “advancing public health by helping to speed innovations that make medicines … more effective, safer, and more affordable,” and “helping the public get the accurate, science-based information they need to use medicines … to improve their health,”1 the FDA’s decision to approve the Merci Retriever system is of concern. The pathways to approval are reviewed by Felten et al in the accompanying article and are outlined in Figure 1. Figure 1. Potential pathways for device approval. The decision to approve the Merci Retriever was based on data from the MERCI (Mechanical Embolus Removal in Cerebral Ischemia) Trial; the approval was granted through the 510(k) process. The Merci Retriever system includes a flexible nickel titanium (nitinol) wire that obtains a helical shape once it is passed through the tip of the guidance catheter. In practice, the catheter/wire is passed distal to the thrombus, the catheter is removed, and the helical configuration assumed by the wire; the clot is then trapped in the helix and withdrawn from the vasculature (Figure 2). The 510(k) clearance means that the Merci Retriever was felt to be substantially equivalent to a predicate device. In this case, the predicate device was the Concentric Retriever, which itself received 510(k) clearance by the FDA in May 2001 for “use in …